This proposal is part of a long-term study of the reproductive physiology of mosquito vectors. Most mosquitoes require a blood meal to initiate each gonotrophic cycle. The trophocytes of the fat body then synthesize a specific protein, vitellogenin, which accumulates in the maturing oocytes. We have recently completed a study of the ultrastructural characteristics and changes in the trophocytes of "yellow-fever mosquito" Aedes aegypti during a normal vitellogenic cycle. We now propose to investigate the endocrine mechanisms controlling the onset of vitellogenin synthesis as well as the termination of synthesis. We plan to combine microsurgical experiments, in which we have extensive experience, e.g., allatectomy, removal of the neurosecretory cells in the brain, ovariectomy, transplantation of these tissues, parabiosis, with immunofluorescence and electron microscopy, with which we are equally experienced. We use a highly sensitive video-enhanced fluorescence microscope to detect the initiation of vitellogenin synthesis. In addition to our work with A. aegypti, we have preliminary results with A. atropalpus. One question arising from these data is whether the first gonotrophic cycle, which is independent of blood-feeding, is controlled in the same way as the subsequent blood-dependent cycles. Mosquito ovaries appear to be the source of the hormone ecdysone in the adult, but its function in vitellogenesis is controversial. One group contends that ovarian ecdysone initiates vitellogenin synthesis by the trophocytes. While ecdysone may play some part in stimulating synthesis, our data indicate that a neurosecretory factor is also essential. We hope to resolve this controversy with the experiments described in this proposal.